Safety and Efficacy of Tenofovir Alafenamide to Prevent Perinatal Transmission of Hepatitis B (TAF-PPT): A Multicentre, Prospective, Open-label, Randomized Controlled Trial
试验速览
- 阶段
- 4 期
- 发起方
- 入组人数
- 240
- 主要终点
- Birth defects.
研究概览
简要总结
To investigate the safety and efficacy of tenofovir alafenamide (orally 25 mg per day) treated in inactive chronic hepatitis B virus (HBV)-infected pregnant women with high viral load from the late pregnancy until the delivery date or postpartum 1 month.
详细描述
The investigators intend to include 240 inactive chronic hepatitis B virus (HBV)-infected pregnant women who have an HBV DNA level higher than 200,000 IU per milliliter. Participants will be randomly assigned, in a 1:1 ratio, to receive tenofovir alafenamide (orally 25 mg per day) from the late pregnancy until the delivery date or postpartum 1 month. All the infants will receive standard immunoprophylaxis (100 IU of hepatitis B immunoglobulin and 10 μg of hepatitis B vaccine within 12 hours of birth; the second injection of 10 μg of HBV vaccine will inject at 1 month; and the third dose of 10 μg of HBV vaccine will give at 6 months). The pregnant women and their infants will be followed until postpartum month 7. The primary outcomes are the birth defects and rates of perinatal transmission of HBV. During the prenatal period or the postnatal period up to 7 months of age, cases of a structural defect in newborns or infants were reported as birth defects. The rate of perinatal transmission was defined as the proportion of infants who are positive for hepatitis B surface antigen at 7 months of age. The secondary safety outcomes are the occurrence of maternal or infant adverse events during the study period. Maternal safety evaluations mainly include any adverse events and complications, hepatitis B virologic breakthrough, alanine aminotransferase flare, and so on. Infant' safety profiles mainly included Apgar scores at 1 minute, any abnormal conditions during the study period, and anthropometric indexes at birth and 7 months of age. The secondary efficacy outcomes are the percentages of mothers with an HBV DNA level of less than 200,000 IU per milliliter just before or at delivery, and the hepatitis B e antigen and surface antigen loss or seroconversion in mothers at postpartum month 7.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 20 Years 至 40 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Gestational age of more than 30 weeks;
- •Had chronic hepatitis B virus (HBV) infection;
- •HBV DNA > 200,000 IU/ml;
- •Consecutively normal levels of alanine aminotransferase (< 40 U/L) and total bilirubin (< 17.1 μmol/L);
- •Willing and able to provide written informed consent and adhere to the trial protocol.
排除标准
- •Previous treatment to reduce alanine aminotransferase and total bilirubin levels;
- •Previous antiviral treatment for HBV infection (except when antiviral agents were administered for the prevention of perinatal transmission during a previous pregnancy and discontinued more than 6 months before the current pregnancy);
- •Coinfection with hepatitis C, D, E, or human immunodeficiency virus;
- •Previous or current evidence of hepatocellular carcinoma, cirrhosis, systemic or other organ disorders;
- •A hemoglobin level of less than 80 g/L;
- •A neutrophil count of less than 1.0 × 10^9/L;
- •An albumin level of less than 30 g/L;
- •Clinical signs of threatened miscarriage;
- •Evidence of fetal deformity by ultrasound examination and other tests;
- •A history of abortion, pregnancy loss, or congenital malformation in a previous pregnancy;
- •A history of genetic disease(s), including the family member(s);
- •Concurrent treatment with other drugs, including but not limited to nephrotoxic drugs, immune modulators, cytotoxic drugs, nonsteroidal antiinflammatory drugs, or steroids.
研究组 & 干预措施
Arm 1
Tenofovir alafenamide fumarate discontinued at delivery date.
干预措施: Tenofovir Alafenamide fumarate 25mg Oral Tablet (Drug)
Arm 2
Tenofovir alafenamide fumarate discontinued at postpartum month 1.
干预措施: Tenofovir Alafenamide fumarate 25mg Oral Tablet (Drug)
结局指标
主要结局
Birth defects.
时间窗: From prenatal tenofovir alafenamide exposure to the birth and postnatal period up to 7 months of age.
Structural defect in newborns or infants were reported as birth defects. The monitoring of birth defects was conducted by a clinical examination during each visit, and further clinical imaging or other tests were performed if indicated. The birth defect rate represented the proportion of infants with a defect among all live births.
The rate of perinatal transmission of hepatitis B virus.
时间窗: At 7 months of age.
The rate of perinatal transmission was defined as the proportion of infants who are positive for hepatitis B surface antigen at 7 months of age.
次要结局
- Hepatitis B surface antigen status.(At postpartum month 7.)
- HBV DNA level.(Immediately before or at delivery.)
- Hepatitis B e antigen status.(At postpartum month 7.)
- Adverse events.(From prenatal tenofovir alafenamide exposure to the delivery (birth) and postnatal period up to 7 months (of age).)
- Alanine aminotransferase flare.(At postpartum month 7.)
- Infants' growth.(At birth and 7 months of age.)
研究者
Qing-Lei Zeng
Associate Professor
The First Affiliated Hospital of Zhengzhou University